The present invention relates to catalytic asymmetric hydrogenation of phosphorus analogs of itaconic acid to synthesize novel optically active phosphono succinates. These are essentially pure novel phosphono succinates having optical activity and are useful as intermediates for the preparation of phosphorus containing pseudopeptides having physiological activity, for example, pharmacological activity. See J. Med. Chem. 31, pp. 1772 (1988).
Preparation of optically active compounds by asymmetric hydrogenation are included in the copending applications U.S. Ser. No. 07/898,853 filed Jun. 15, 1992 and U.S. Ser. No. 07/898,253 filed Jun. 15, 1992. These applications review relevant references and are, therefore, hereby incorporated by reference.
Copending application U.S. Ser. No. 07/898,853 discloses chiral alpha-amino ketones in which the --CONH-- linkage has been replaced by a --COCH.sub.2 -- and a process for the preparation which provides a wide range of side chains. Copending application U.S. Ser. No. 07/898,253 discloses both novel alpha-amino phosphonates and a process having sufficient flexibility for use in making the phosphonates. However, the present invention uses phosphorus analogs of itaconic acid to provide novel compounds and process therefor.
The following references relate to the preparation of optically active succinic acid derivatives: JP 54122219-A abstracted in Derwent No. 79835B/44; JP 54057490-A abstracted in Derwent No. 46194/25; JP 54128511-A abstracted in Derwent No. 83174/46; JP 3101638 abstracted in Derwent No. 91-168387/23. U.S. Pat. No. 4,922,006 discloses the hydrogenation of 2,3-dehydrophosphinothricine derivatives using a ruthenium, rhodium or iridium complex of phosporus containing catalyst. U.S. Pat. No. 4,939,288 discloses asymmetric catalytic hydrogenation of a 2(E)-alkylidene succinate derivative in the presence of a rhodium complexed (R,R)-bisphosphine compound.
U.S. Pat. No. 4,016,148 discloses peptide derivatives having a moiety characterized by the replacement of the carboxyl group of a naturally occurring L alpha-amino acid by a phosphorus group including a --P(O)(OH).sub.2 group.
Optically active alpha-amino phosphonates are useful as antibiotics and/or are useful in the preparation of phosphorus-containing analogs of peptides, i.e., --P(O)(OH).sub.2 replaces a --CONH.sub.2 group to provide phosphono peptides or pseudopeptides, having known uses. For example, such phosphorus-type compounds have been shown to be effective as antibiotics, antibiotic enhancers, or enzyme inhibitors.
The flexibility of the present synthesis permits the synthesis of analogues of unexpectedly pure chiral phosphono succinate derivatives, ie a peptide-like compound having the --CONH-- replaced by --COCH.sub.2 -- and another amino group replaced by a phosphono group, also having a wide range of substituents.
As discussed above the literature is replete with examples of novel amino acid side chains designed to impart improved biological properties to peptides and pseudopeptide molecules. Thus, the present novel compounds are useful as intermediates to make products or may be themselves products having such biological properties.